Project Summary/ Abstract Although only 25% of US adults have multiple chronic conditions, people with multiple conditions account for 71% of US healthcare spending. However, not all people experience the same symptoms or progression of their multiple chronic conditions. This variability is partially due to environmental and psychosocial factors including self-efficacy which is the confidence to successfully perform specific behaviors and influence specific life domains. Cellular and systemic changes also accompany chronic disease progression including Interleukin 6 (IL-6) and tumor necrosis factor alpha receptor 1 (TNF?R1), brain derived neurotropic factor (BDNF) and heart rate variability (HRV). The effect of self-efficacy on health behavior has been widely studied, but there is a gap in what is known about the direct effect of self-efficacy on physiologic mechanisms, especially in people with multiple chronic conditions. This applicant's previous research showed an association between IL-6 and coping self-efficacy in two cross-sectional studies (N=48 & N=160) of older adults with at least one chronic disease. Further mechanistic research is needed to explore the associations between coping self-efficacy and the stress response networks. Therefore, the purpose of this 2-year diversity supplement is to evaluate the associations and pre-post intervention changes between coping self-efficacy and physiologic stress indices (IL-6, TNF?R1, BDNF, HRV) in community-dwelling adults with multiple chronic conditions. Recruitment will be embedded within the current PROMOTE center-affiliated pilot studies (N=115). Utilizing 3 PROMOTE P30 pilots presents an opportunity to concurrently evaluate coping self-efficacy and physiologic stress indices within each study, between studies and in pooled data across the 3 studies. The proposed study builds upon the strengths of the individual pilot studies by adding a coping self-efficacy measurement and a more diverse array of physiologic measures of the stress response network, including heart-rate variability, certain pro-inflammatory cytokines (IL-6 and TNF?R1) and BDNF. Understanding the physiologic mechanisms of self-efficacy may reveal new ways to measure it as an outcome of self- efficacy based interventions. Adding biologic data to the study of self-efficacy may influence policy change toward re- imbursement, accessibility and streamlining self-efficacy based interventions into mainstream healthcare settings. With large numbers of adults with multiple chronic conditions and the resulting economic costs, this research contributes to the goal of reducing the chronic disease burden in this country.